In this talk, we're going to
cover a very common entity
inflammation of the gastric mucosa.
Let's get into
As he said,
it's a very common entity overall.
The prevalence is probably higher but
approximately 6 per 100,000 population.
And it's higher in
where there may be a greater
infectious agent burden.
When we talk about
most commonly we're talking
about Helicobacter pylori.
So aspire keep, and there will
be, as I've already indicated,
a higher prevalence of this particular
infection in developing countries,
but also occurs in the
Another form of gastritis
is autoimmune gastritis.
So an autoimmune disease more
commonly associated with women,
and it does the incidence
does increase with age.
Let's talk about
There are various ways
that one can get gastritis.
Infection is probably the
most common and again,
Helicobacter pylori is the most
common of the infectious causes.
That is about the third time when I've
said it, so probably is important.
But there are other other bacterial
and viral agents that can do this.
particularly within the
can be a cause of an
another very common GI bacterium.
Herpes simplex and cytomegalovirus
are viral etiologies for gastritis.
I've already mentioned
typically in women and
in the older population.
And it's associated
specifically with biomarkers
that we can measure anti-parietal
And these will be causes of additional
pathologies that we'll cover very shortly.
There are other
less common causes.
I wouldn't say they're exactly rare,
but less common causes of gastritis.
This includes Crohn's disease,
so an inflammatory bowel disorder
that, in fact,
can affect any part of the GI tract
and can cause a gastritis
within the stomach.
certain to the vasculitis,
And then other forms
less common of gastritis,
that are either collagenous
gastritis, eosinophilic gastritis,
or ischemic gastritis,
often caused by certain
medications that we'll get into.
The stomach is just
not a uniform bag.
In fact, there are
different areas within it
where the esophagus
joins, there's the cardia,
the very dome of the
stomach is the fundus.
The corpus or the main
body of the stomach
has a particularly
large surface area,
and is involved with majority
of what the stomach does.
And then in the antrum, near the
pyloric sphincter is a separate area.
In all of these areas.
there's different histology.
And for the most part,
when we talk about gastritis,
although it can affect
any part of the stomach,
we're mostly going to be
talking about the antrum.
So why does this have any
impact or why do we care?
What I'm showing you here within
the main corpus of the stomach
is the typical organization.
It is a simple columnar epithelium
that's thrown up into very prominent
villi with deep deep pits.
If we look at this in a
different kind of organization,
you can see that near the top where
there's a lot of kind of cleared out cells,
that's where we're
going to have mucus,
and that's going to be protective to
the epithelium throughout the stomach.
The middle zone, which looks a little
bit pinker on the left hand side
are going to be
the parietal cells.
Those are going to be the cells
responsible for the most part
for making the gastric
acid, the hydrochloric acid,
they're also going to
make intrinsic factor.
And then the chief cells,
they're going to be making a
zymogen pepsinogen at the base
they're going to be making a
zymogen pepsinogen at the base
that is going to be eventually
processed to make pepsin
which is going to be part of the digestive
enzymes necessary for getting food
turned into smaller metabolites
that can be absorbed.
That's up in the main corpus.
As we look down into the antrum,
we have a slight modification
of the overall architecture.
We have many,
many more mucus cells.
Well, this makes sense because we've
been accumulating throughout the corpus,
all that gastric acidity.
So we're going to need to
protect within the pylorus.
So we're going to need to
protect within the pylorus.
The cells that are there,
the epithelium that's there,
so we're going to need
to make more mucus.
In this zone as well, we don't need
them have as many parietal cells,
but we will have more stem cells
that are going to turn into
the parietal cells and other
elements within the GI epithelium.
And then deep within that structure,
there is gonna be more mucus cells.
So this is going to be the
area where inflammation
is going to have a major impact.
And we're not going
to have as much mucus
and this is where we're going
to get the most damage overall.
Looking at this histologically,
it doesn't have that same kind
of light pink and then bluer
organization that we
saw on the corpus.
It's more mostly mucus glands.
And then within
the lamina propria
around the individual glands,
we're gonna see more inflammatory cells.
And that's going to be very characteristic
when we talk about the gastritis.
So shown here on the
right hand side now
is a schematic where you can
see the various elements,
the mucous neck
cells at the top,
the stem and the preparietal cells in
the middle in the deeper mucus cells.
And in the lamina propria,
we've expanded it,
and in there are lymphocytes and
macrophages and some cases, neutrophils
that are going to be part of
an inflammatory infiltrate
causing damage that appearance
where we've dropped out cells.
We have lost epithelium
and that's going to be part
and parcel of what goes on
with the inflammatory
So how is this happening,
that kind of a global higher level look?
Well, you could have
increased acid production.
So you may have more
that is driving
So the parietal cells
up in the corpus
are going to be cranking
out more hydrochloric acid.
You may have diminished
There a variety of reasons for this,
some of it can be genetic and intrinsic.
Others can be driven
by certain drugs
that cause a diminished vascular supply
to the GI tract into the stomach.
You can have direct injury
to the epithelial cells
or effects on the
And this is what I was talking about the
nonsteroidal anti-inflammatory drugs,
although you think they
would be anti-inflammatory,
they also cause constriction
of the micro vasculature.
So you do not get the normal
blood flow to the gastric mucosa.
And therefore, you're not making
the normal levels of mucus,
and therefore you're not
getting appropriate protection.
An alcoholic gastritis can cause
a direct injury to the epithelium
that's making the mucus.
So those cells go, "I give up."
And you don't have enough mucus
to coat the rest of the stomach.
In autoimmune disease,
you have specifically targeted lymphocytes
that recognize typically
and they will in turn drive the
production of autoantibodies.
So you have other antibodies and T cells
directed against the parietal cells.
So, you are influencing the
production of gastric acid,
but you also have some secondary
injury due to cytokines
and the activation
that will cause destruction of
other parts of the epithelium,
in particular, the mucous cells.
And then infection.
Back to Helicobacter pylori,
our favorite little
So it is a flagellated
It really does have kind of a spiral
shape, that's kind of cool.
And it has the ability to
spin and to move quite well
within the mucous that
lines the stomach.
And it can chemotax to
colonize underneath the mucosa.
So it's a clever little devil.
It makes a number of things that are going
to be particularly toxic to the epithelium.
So one is urease,
this in some cases,
in many cases will neutralize
the gastric acidity,
but it causes direct mucosal injury by
increasing the production of ammonia.
On its surface,
it has a number of lipopolysaccharides.
And those are going to be very
activating for the innate immune system
in particular macrophages,
so that's going to drive
the inflammatory response.
And then, just for the heck of it,
it secretes a variety of exotoxins.
So these have various names.
I don't think that those are particularly
important for you to remember.
But the vacuolating toxin
causes gastric mucosal injury.
In addition to secretory enzymes,
things that break down the mucin.
Oh, wow. If your mucous
layer has been degraded,
you don't have as
good of protection.
They make proteases that can cause
injury to the epithelial cells.
They will cause direct gastric mucosal
injury through the elaboration of lipases.
They do have an additional structure that
allows them to inject various effectors.
So a Pilli-like structure.
So basically a little probe
that can sidle up to cells,
and inject things
directly into them.
And then as part of the exotoxins
and the other effectors,
there are others, the cagA complex
that will cause actin remodeling
within cells so that allows the
organism to move around within the cell.
They will also induce the
production of interleukin 8
which is a potent chemotactic
agents specifically for neutrophils.
They can induce
and also the apoptosis inhibition
of the epithelial cells.
So while they're damaging them and
eliciting an inflammatory response,
they're also potentially
So, long term chronic infection
with Helicobacter pylori
can also be something that drives
the development of malignancy.
So in acute gastritis
is an antral-predominant
So remember I said most
of the inflammation
is going to be happening
down in the antrum.
Increased gastrin production and
diminish the amount of statin production
will lead to increased
and that increased acid secretion
exacerbates mucosal injury
and associated inflammation.
With chronic gastritis,
so going on for
months and even years,
with injury, the glands will
become progressively atrophic.
And there is a response of the
epithelium to try to combat to push back
on all of the damage
that's going on.
And one of the changes is
the conversion of metaplasia
to a more intestinal
sort of epithelium,
not like the normal gastric
epithelium, but intestinal,
which theoretically can better
tolerate the conditions that are there.
As we injure the parietal cells, we'll
have actually a diminished acid production.
And that hypochlorhydria means that
we're not going to absorb iron.
So we will eventually develop
an iron deficiency anemia
when we have chronic gastritis.
As we damage the
parietal cells as well,
we're not making
intrinsic factors much.
And without intrinsic factor,
we can't absorb ultimately B12.
And so we end up with
a B12 deficiency.
I've already indicated that with now
proliferation, diminished apoptosis,
ongoing inflammation with all those
evil, inflammatory mediators,
we're increasing the risk for
developing gastric adenocarcinoma.
And with all that inflammation,
we can actually develop an
increased risk for a lymphoma,
a mucosa-associated lymphoid
tissue or MALT lymphoma.
And you may have already
experienced some of this yourself,
but it's predictable
in many ways.
So early on,
it may be completely asymptomatic,
that there may be some dyspepsia
of so there may be heartburn,
or feelings of reflux.
There may be abdominal
pain with bleeding,
because of damage to the epithelium,
you may have hematemesis.
So meaning vomiting blood,
or you may have dark, tarry stools,
so blood within the stomach.
By the time it goes through
the entire GI tract,
you have black,
sticky, tarry stools.
And clearly you're losing blood,
so you would develop an
iron deficiency anemia.
But that's compounded by the fact that you
are not making enough hydrochloric acid
to allow normal iron absorption.
Because we are injuring
the parietal cells,
you may also develop
the B12 deficiency
because you're not making
an intrinsic factor.
And so all of the normal symptoms
associated with B12 deficiency,
fatigue, inflammation of
the tongue and oropharynx,
a cognitive decline other
all B12 deficiency-associated
symptoms may also soon pervane.
Making the diagnosis
then of gastritis.
So we're going to want to
do a complete blood count.
if you have a microcytic anemia,
that means you probably have reduced
iron, makes sense.
If you have a macrocytic anemia that
suggests that you have a B12 deficiency.
You want to look in
the stool for blood.
You would definitely want
to do endoscopy and biopsy
and that would help you
to establish the etiology.
Is it Helicobacter?
Is it something else?
Is it eosinophilic gastritis,
one of those other entities?
If you're thinking and the vast
majority of these gastroenteritis
are going to be due to
you can do certain other tests.
So there's a urea breath test.
Remember that the
Helicobacter makes urease,
which will allow us
to break down urea.
You can actually measure those
metabolites in the breath.
You can do a fecal
antigen test looking for
antigens within the stool
and you can do serologies.
The serologies would
may only indicate
you've had a prior
Helicobacter pylori infection.
It may not necessarily
mean you have one now,
but a positive breath test and/or
a positive fecal antigen test
means you've got ongoing
Helicobacter pylori infection.
You may look for autoantibodies
in that autoimmune gastritis
and look for autoantibodies directed
against parietal cells or intrinsic factor
that will allow you to make
that particular diagnosis.
And you would treat
these quite differently.
With an infection,
we're going to treat the infection.
With autoimmune disease, we're actually
going to give immunosuppression.
So both sides of the coin.
How do we manage this?
Well, it depends on
your final diagnosis.
In general, we want to avoid
any additional toxicity.
So tell your patients to avoid alcohol
which causes direct mucosal injury,
and will also
dissolve the mucin.
Over the surface, you want to stay away
from nonsteroidal anti-inflammatory drugs,
which will cause spasm
in the microvasculature,
so you're not getting
good blood supply.
You would want to get proton pump
inhibitors to limit the amount of damage
happening due to the gastric
acidity, the hydrochloric acid.
you want to replace B12.
You want to replace iron
so that you can treat
those particular problems
associated with the anemia,
but B12 so you don't develop chronic
long term neurologic deficits.
And then, if you make the diagnosis of
Helicobacter pylori, you go after it.
Lot of therapies, we're pretty good
at treating this now we can clear it.
In many areas in developing countries
where sanitary conditions are not optimal,
it may recur over
and over again.
But the therapies
that you want to give
are basically proton pump inhibitors
to limit gastric acid secretion,
and then a combination
of various antibiotics.
The triple therapy are
three different antibiotics,
a quadruple therapy
as in bismuth.
And it turns out that
bismuth containing compounds
are bactericidal for
And with that, a very long talk about
a very common entity, gastritis.